Ceftazidime/avibactam

Ceftazidime/avibactam
Combination of
Ceftazidime	Cephalosporin antibiotic
Avibactam	β-lactamase inhibitor
Clinical data
Trade names	Avycaz, Zavicefta, others
AHFS/Drugs.com	Monograph
MedlinePlus	a615018
License data	US DailyMed: Ceftazidime avibactam;
Pregnancy; category	AU: B3; ;
Routes of; administration	Intravenous infusion
ATC code	J01DD52 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); US: ℞-only; EU: Rx-only;
Identifiers
CAS Number	1393723-27-7;
PubChem CID	90643431;
KEGG	D10779;
	(what is this?)

Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor.^[4] It is used to treat complicated intra-abdominal infections, urinary tract infections, and pneumonia.^[4]^[5] It is only recommended when other options are not appropriate.^[4] It is given by infusion into a vein.^[4]

Common side effect include nausea, fever, liver problems, headache, trouble sleeping, and pain at the site of infusion.^[4] Severe side effects may include anaphylaxis, seizures, and Clostridioides difficile-associated diarrhea.^[4] While use appears to be safe in pregnancy the medication has not been well studied in this group.^[6] Doses should be adjusted in those with kidney problems.^[7] Ceftazidime works by interfering with the building of the bacterial cell wall while avibactam works by preventing ceftazidime's breakdown.^[4]

The combination was approved for medical use in the United States and the European Union in 2015.^[4]^[5] It is on the World Health Organization's List of Essential Medicines.^[8] Resistances are increasingly been reported with United States, Greece and Italy accounting for 80% of cases.^[9]

Medical use

Ceftazidime/avibactam is used to treat certain multidrug-resistant gram-negative infections.^[10]

Ceftazidime/avibactam is used for the treatment of:

complicated intra-abdominal infections. In these cases it is often used in combination with metronidazole, which provides coverage for anaerobic pathogens.^[7]
complicated urinary tract infections, including acute pyelonephritis, in adults.
hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.^[11]

Bacterial activity

For many bacterial infections, it offers little or no advantage over ceftazidime monotherapy, due to the widespread expression of resistance mechanisms other than β-lactamase production. These include Haemophilus, Moraxella and Neisseria pathogens, and infections caused by Acinectobacter baumannii.^[10]

The antibacterial spectrum of ceftazidime/avibactam includes nearly all Enterobacteriaceae, including ceftazidime-resistant strains. The activity of ceftazidime/avibactam against the important hospital pathogen Pseudomonas aeruginosa is variable, due to the potential presence of other resistance mechanisms in addition to β-lactamase production. Synergy was observed for avibactam with ceftazidime in Burkholderia infections.^[12]

Adverse events

When used to treat life-threatening infections, ceftazidime/avibactam is more likely than carbapenem antibiotics to cause serious adverse events, including worsening kidney function and gastrointestinal adverse effects.^[13]

Mechanism of action

Bacterial resistance to cephalosporins is often due to bacterial production of β-lactamase enzymes that deactivate these antibiotics. Avibactam inhibits some (but not all) bacterial β-lactamases. Also, some bacteria are resistant to cephalosporins by other mechanisms, and therefore avibactam doesn't work. Avibactam is not active against New Delhi metallo-β-lactamase 1 (NDM-1).^[14] Avibactam inhibits Klebsiella pneumoniae carbapenemases (KPCs), and AmpC-type β-lactamases, which are resistant to the other clinically available β-lactamases, tazobactam and clavulanic acid.^[15]

Regulatory

It was granted approval for marketing in the United States by the Food and Drug Administration (FDA) in February 2015.^[16] It was granted approval for marketing in Europe by the European Medicines Agency in 2016. During its clinical development, ceftazidime/avibactam was designated as a Qualified Infectious Disease Product under the Generating Antibiotic Incentives Now provision of the Food and Drug Administration Safety and Innovation Act.^[17]^[18] Development of ceftazidime/avibactam was fast-tracked by the FDA due to the shortage of drugs for treatment of infections due to antibiotic-resistant bacteria.^{[citation needed]}

References

^ "Briefing package: ceftazidime-avibactam. Anti-infective drugs advisory committee meeting" (PDF). U.S. Food and Drug Administration (FDA). Archived from the original (PDF) on 30 June 2015. Retrieved 27 June 2015.
^ "Avycaz- ceftazidime, avibactam powder, for solution". DailyMed. 26 January 2024. Retrieved 21 February 2024.
^ "Zavicefta EPAR". European Medicines Agency. 23 June 2016. Retrieved 21 February 2024.
^ ^a ^b ^c ^d ^e ^f ^g ^h "Ceftazidime and Avibactam Sodium Monograph for Professionals". Drugs.com. Retrieved 25 October 2019.
^ ^a ^b "Application for inclusion of ceftazidime-avibactam" (PDF). WHO. Retrieved 25 October 2019.
^ "Avibactam / ceftazidime (Avycaz) Use During Pregnancy". Drugs.com. Retrieved 25 October 2019.
^ ^a ^b Mosley JF, Smith LL, Parke CK, Brown JA, Wilson AL, Gibbs LV (August 2016). "Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal and Urinary Tract Infections". P & T. 41 (8): 479–483. PMC 4959616. PMID 27504064.
^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^ Di Bella S, Giacobbe DR, Maraolo AE, Viaggi V, Luzzati R, Bassetti M, et al. (June 2021). "Resistance to ceftazidime/avibactam in infections and colonisations by KPC-producing Enterobacterales: a systematic review of observational clinical studies". Journal of Global Antimicrobial Resistance. 25: 268–281. doi:10.1016/j.jgar.2021.04.001. hdl:11368/2990131. PMID 33895414. S2CID 233399477.
^ ^a ^b Lagacé-Wiens P, Walkty A, Karlowsky JA (2014). "Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections". Core Evid. 9: 13–25. doi:10.2147/CE.S40698. PMC 3908787. PMID 24493994.
^ "Highlights of prescribing information". allergan.com. Retrieved 22 July 2023.
^ Mushtaq S, Warner M, Livermore DM (2010). "In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other non-fermenters". J Antimicrob Chemother. 65 (11): 2376–2381. doi:10.1093/jac/dkq306. PMID 20801783.
^ Sternbach N, Leibovici Weissman Y, Avni T, Yahav D (August 2018). "Efficacy and safety of ceftazidime/avibactam: a systematic review and meta-analysis". J. Antimicrob. Chemother. 73 (8): 2021–2029. doi:10.1093/jac/dky124. PMID 29659836.
^ Lohans CT, Brem J, Schofield CJ (December 2017). "New Delhi Metallo-β-Lactamase 1 Catalyzes Avibactam and Aztreonam Hydrolysis". Antimicrob. Agents Chemother. 61 (12). doi:10.1128/AAC.01224-17. PMC 5700305. PMID 28971873.
^ "Clinical Review, NDA 206494, Ceftazidime-avibactam" (PDF). Food and Drug Administration (FDA). 2015-02-18.
^ "AVYCAZ (ceftazidime-avibactam) approval letter" (PDF). Food and Drug Administration (FDA). 2015-02-25. Retrieved September 10, 2019.
^ "FDA approves new antibacterial drug Avycaz" (Press release). Food and Drug Administration (FDA). Archived from the original on 2015-11-17. Retrieved 2015-11-16.
^ "FDA clears Actavis' combination antibacterial Avycaz". FirstWord Pharma. Retrieved 2015-11-16.

[FDA2015-1] "Briefing package: ceftazidime-avibactam. Anti-infective drugs advisory committee meeting" (PDF). U.S. Food and Drug Administration (FDA). Archived from the original (PDF) on 30 June 2015. Retrieved 27 June 2015.

[2] "Avycaz- ceftazidime, avibactam powder, for solution". DailyMed. 26 January 2024. Retrieved 21 February 2024.

[Zavicefta_EPAR-3] "Zavicefta EPAR". European Medicines Agency. 23 June 2016. Retrieved 21 February 2024.

[AHFS2019-4] ^ ^a ^b ^c ^d ^e ^f ^g ^h "Ceftazidime and Avibactam Sodium Monograph for Professionals". Drugs.com. Retrieved 25 October 2019.

[WHO2019-5] "Application for inclusion of ceftazidime-avibactam" (PDF). WHO. Retrieved 25 October 2019.

[Preg2019-6] "Avibactam / ceftazidime (Avycaz) Use During Pregnancy". Drugs.com. Retrieved 25 October 2019.

[PT2016-7] Mosley JF, Smith LL, Parke CK, Brown JA, Wilson AL, Gibbs LV (August 2016). "Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal and Urinary Tract Infections". P & T. 41 (8): 479–483. PMC 4959616. PMID 27504064.

[WHO21st-8] World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.

[9] Di Bella S, Giacobbe DR, Maraolo AE, Viaggi V, Luzzati R, Bassetti M, et al. (June 2021). "Resistance to ceftazidime/avibactam in infections and colonisations by KPC-producing Enterobacterales: a systematic review of observational clinical studies". Journal of Global Antimicrobial Resistance. 25: 268–281. doi:10.1016/j.jgar.2021.04.001. hdl:11368/2990131. PMID 33895414. S2CID 233399477.

[Ceftazidime-avibactam:_an_evidence-10] Lagacé-Wiens P, Walkty A, Karlowsky JA (2014). "Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections". Core Evid. 9: 13–25. doi:10.2147/CE.S40698. PMC 3908787. PMID 24493994.

[11] "Highlights of prescribing information". allergan.com. Retrieved 22 July 2023.

[12] Mushtaq S, Warner M, Livermore DM (2010). "In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other non-fermenters". J Antimicrob Chemother. 65 (11): 2376–2381. doi:10.1093/jac/dkq306. PMID 20801783.

[13] Sternbach N, Leibovici Weissman Y, Avni T, Yahav D (August 2018). "Efficacy and safety of ceftazidime/avibactam: a systematic review and meta-analysis". J. Antimicrob. Chemother. 73 (8): 2021–2029. doi:10.1093/jac/dky124. PMID 29659836.

[14] Lohans CT, Brem J, Schofield CJ (December 2017). "New Delhi Metallo-β-Lactamase 1 Catalyzes Avibactam and Aztreonam Hydrolysis". Antimicrob. Agents Chemother. 61 (12). doi:10.1128/AAC.01224-17. PMC 5700305. PMID 28971873.

[15] "Clinical Review, NDA 206494, Ceftazidime-avibactam" (PDF). Food and Drug Administration (FDA). 2015-02-18.

[16] "AVYCAZ (ceftazidime-avibactam) approval letter" (PDF). Food and Drug Administration (FDA). 2015-02-25. Retrieved September 10, 2019.

[17] "FDA approves new antibacterial drug Avycaz" (Press release). Food and Drug Administration (FDA). Archived from the original on 2015-11-17. Retrieved 2015-11-16.

[18] "FDA clears Actavis' combination antibacterial Avycaz". FirstWord Pharma. Retrieved 2015-11-16.

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Ceftazidime/avibactam

Medical use

Bacterial activity

Adverse events

Mechanism of action

Regulatory

References

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